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Transient Protective Effect of B-Vitamins in Experimental Epilepsy in the Mouse Brain

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Abstract

The regulation of programmed cell death in the nervous system of vertebrates is a complex mechanism aimed to remove superfluous or damaged cells. Epileptic seizures can lead to an activation of pathways resulting in neuronal cell death. B-vitamins might have a neuroprotective potential reducing cell death following appropriate stimulation. Here, the role of the B-vitamins B1 (thiamine), B6 (pyridoxine), and B12 (cobalamine) was investigated in a mouse model of experimental epilepsy induced by kainate. B-vitamin pre-treated animals showed a significantly reduced epileptic score during the first 15 min after kainate injection. The molecular response to kainate showed a bi-phased time course with early induction of Bcl-2 expression within 12 h and a second induction after 7 days of kainate exposure. B-vitamin pre-treatment resulted in significant higher Bcl-2 expression in control animals (no kainate) and at 12 h within the early phase. Bcl-2 expression was not affected by B-vitamins within the second phase. BAX expression was not significantly influenced during the whole experiment. Three days after kainate stimulation, the number of TdT-mediated dUTP-biotin nick end labeling-positive cells in the hippocampal region was lower in B-vitamin-treated animals. Therefore, B-vitamin pre-treatment may attenuate the response to epileptic stimulation.

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References

  • Ananth C, Thameem Dheen S, Gopalakrishnakone P, Kaur C (2001) Domoic acid-induced neuronal damage in the rat hippocampus: changes in apoptosis related genes (bcl-2, bax, caspase-3) and microglial response. J Neurosci Res 66:177–190

    Article  CAS  PubMed  Google Scholar 

  • Apeland T, Froyland ES, Kristensen O, Strandjord RE, Mansoor MA (2008) Drug-induced pertubation of the aminothiol redox-status in patients with epilepsy: improvement by B-vitamins. Epilepsy Res 82:1–6

    Article  CAS  PubMed  Google Scholar 

  • Balk E, Chung M, Raman G, Tatsioni A, Chew P, Ip S et al (2006) B vitamins and berries and age-related neurodegenerative disorders. Evid Rep/Technol Assess 134:1–161

    Google Scholar 

  • Chuang JI, Chen ST, Chang YH, Jen LS (2001) Alteration of Bcl-2 expression in the nigrostriatal system after kainate injection with or without melatonin co-treatment. J Chem Neuroanat 21:215–223

    Article  CAS  PubMed  Google Scholar 

  • Dakshinamurti K, Sharma SK, Bonke D (1990) Influence of B vitamins on binding properties of serotonin receptors in the CNS of rats. Klin Wochenschr 68:142–145

    Article  CAS  PubMed  Google Scholar 

  • Dominguez YL, Hernandez M, Matos CM, Zhou D (2006) Is B vitamins deficiency associated with prevalence of Alzheimer’s disease in Cuban elderly? Nutr Health 18:103–118

    CAS  PubMed  Google Scholar 

  • Gavrieli Y, Sherman Y, Ben Sasson SA (1992) Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation. J Cell Biol 119:493–501

    Article  CAS  PubMed  Google Scholar 

  • Gillardon F, Wickert H, Zimmermann M (1995) Up-regulation of bax and down-regulation of bcl-2 is associated with kainate-induced apoptosis in mouse brain. Neurosci Lett 192:85–88

    Article  CAS  PubMed  Google Scholar 

  • Hockenbery D, Nunez G, Milliman C, Schreiber RD, Korsmeyer SJ (1990) Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death. Nature 348:334–336

    Article  CAS  PubMed  Google Scholar 

  • LeBlanc AC (2003) Natural cellular inhibitors of caspases. Prog Neuropsychopharmacol Biol Psychiatry 27:215–229

    Article  CAS  PubMed  Google Scholar 

  • Lopez E, Pozas E, Rivera R, Ferrer I (1999) Bcl-2, Bax and Bcl-x expression following kainic acid administration at convulsant doses in the rat. Neuroscience 91:1461–1470

    Article  CAS  PubMed  Google Scholar 

  • Mikati MA, Zeinieh M, Habib RA, El Hokayem J, Rahmeh A, El Sabban M et al (2008) Changes in sphingomyelinases, ceramide, Bax, Bcl(2), and caspase-3 during and after experimental status epilepticus. Epilepsy Res 81:161–166

    Article  CAS  PubMed  Google Scholar 

  • Mooney S, Leuendorf JE, Hendrickson C, Hellmann H (2009) Vitamin B6: a long known compound of surprising complexity. Molecules 14:329–351

    Article  CAS  PubMed  Google Scholar 

  • Mori F, Okada M, Tomiyama M, Kaneko S, Wakabayashi K (2005) Effects of ryanodine receptor activation on neurotransmitter release and neuronal cell death following kainic acid-induced status epilepticus. Epilepsy Res 65:59–70

    Article  CAS  PubMed  Google Scholar 

  • Obeid R, McCaddon A, Herrmann W (2007) The role of hyperhomocysteinemia and B-vitamin deficiency in neurological and psychiatric diseases. Clin Chem Lab Med 45:1590–1606

    Article  CAS  PubMed  Google Scholar 

  • Scalabrino G, Veber D, Mutti E (2008) Experimental and clinical evidence of the role of cytokines and growth factors in the pathogenesis of acquired cobalamin-deficient leukoneuropathy. Brains Res Rev 59:42–54

    Article  CAS  Google Scholar 

  • Schenkel J (2004) Activation of the c-Jun transcription factor following neurodegeneration in vivo. Neurosci Lett 361:36–39

    Article  CAS  PubMed  Google Scholar 

  • Schulz RJ (2007) Homocysteine as a biomarker for cognitive dysfunction in the elderly. Curr Opin Clin Nutr Metab Care 10:718–723

    Article  CAS  PubMed  Google Scholar 

  • Sinha S, Patil SA, Jayalekshmy V, Satishchandra P (2008) Do cytokines have any role in epilepsy? Epilepsy Res 82:171–176

    Article  CAS  PubMed  Google Scholar 

  • Tagscherer KE, Fassl A, Campos B, Farhadi M, Kraemer A, Bock BC et al (2008) Apoptosis-based treatment of glioblastomas with ABT-737, a novel small molecule inhibitor of Bcl-2 family proteins. Oncogene 27:6646–6656

    Article  CAS  PubMed  Google Scholar 

  • Trovero F, Gobbi M, Weil-Fuggaza J, Besson MJ, Brochet D, Pirot S (2000) Evidence for a modulatory effect of sulbutiamine on glutamatergic and dopaminergic cortical transmissions in the rat brain. Neurosci Lett 292:49–53

    Article  CAS  PubMed  Google Scholar 

  • Tuunanen J, Lukasiuk K, Halonen T, Pitkanen A (1999) Status epilepticus-induced neuronal damage in the rat amygdaloid complex: distribution, time-course and mechanisms. Neuroscience 94:473–495

    Article  CAS  PubMed  Google Scholar 

  • Vezzani A, Balosso S, Ravizza T (2008) The role of cytokines in the pathophysiology of epilepsy. Brain Behav Immun 22:797–803

    Article  CAS  PubMed  Google Scholar 

  • Vogel J, Weigand MA, Behrens A, Wagner EF, Schorpp-Kistner M, Zimmermann M et al (2007) Infarct volume after transient middle cerebral artery occlusion (MCAo) can be reduced by attenuation but not by inactivation of c-Jun action. Brain Res 1151:12–19

    Article  CAS  PubMed  Google Scholar 

  • Vyas S, Javoy-Agid F, Herrero MT, Strada O, Boissiere F, Hibner U et al (1997) Expression of Bcl-2 in adult human brain regions with special reference to neurodegenerative disorders. J Neurochem 69:223–231

    Article  CAS  PubMed  Google Scholar 

  • Wang L, Liu YH, Huang YG, Chen LW (2008) Time-course of neuronal death in the mouse pilocarpine model of chronic epilepsy using Fluoro-Jade C staining. Brain Res 1241:157–167

    Article  CAS  PubMed  Google Scholar 

  • Winter C, Weiss C, Martin-Villalba A, Zimmermann M, Schenkel J (2002) JunB and Bcl-2 overexpression results in protection against cell death of nigral neurons following axotomy. Brain Res Mol Brain Res 104:194–202

    Article  CAS  PubMed  Google Scholar 

  • Wu G, Lu ZH, Wang J, Wang Y, Xie X, Meyenhofer MF et al (2005) Enhanced susceptibility to kainate-induced seizures, neuronal apoptosis, and death in mice lacking gangliotetraose gangliosides: protection with LIGA 20, a membrane-permeant analog of GM1. J Neurosci 25:11014–11022

    Article  CAS  PubMed  Google Scholar 

  • Yalcin A, Kanit L, Sozmen EY (2004) Altered gene expressions in rat hippocampus after kainate injection with or without melatonin pre-treatment. Neurosci Lett 359:65–68

    Article  CAS  PubMed  Google Scholar 

  • Youle RJ, Strasser A (2008) The BCL-2 protein family: opposing activities that mediate cell death. Nat Rev Mol Cell Biol 9:47–59

    Article  CAS  PubMed  Google Scholar 

  • Zaczek R, Simonton S, Coyle JT (1980) Local and distant neuronal degeneration following intrastriatal injection of kainic acid. J Neuropathol Exp Neurol 39:245–264

    Article  CAS  PubMed  Google Scholar 

  • Zhong LT, Sarafian T, Kane DJ, Charles AC, Mah SP, Edwards RH et al (1993) bcl-2 inhibits death of central neural cells induced by multiple agents. Proc Natl Acad Sci U S A 90:4533–4537

    Article  CAS  PubMed  Google Scholar 

  • Zucchini S, Buzzi A, Barbieri M, Rodi D, Paradiso B, Binaschi A et al (2008) Fgf-2 overexpression increases excitability and seizure susceptibility but decreases seizure-induced cell loss. J Neurosci 28:13112–13124

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The authors thank Inge Keller for her expert technical assistance. This work was supported by Merck KGaA, Darmstadt, Germany.

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Authors and Affiliations

  1. Department of Physiology and Pathophysiology, University of Heidelberg Medical School, Im Neuenheimer Feld 326, 69120, Heidelberg, Germany

    Tamer Rabie, Wolfgang Mühlhofer, Alexander T. Bauer, Manfred Zimmermann, Hugo H. Marti & Johannes Schenkel

  2. Institute of Medical Biometry and Informatics, University of Heidelberg Medical School, Heidelberg, Germany

    Thomas Bruckner & Johannes Schenkel

  3. German Cancer Research Centre, Heidelberg, Germany

    Anna Schwab & Johannes Schenkel

  4. Merck KGaA, Darmstadt, Germany

    Dieter Bonke

Authors
  1. Tamer Rabie
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  2. Wolfgang Mühlhofer
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  3. Thomas Bruckner
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  4. Anna Schwab
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  5. Alexander T. Bauer
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  6. Manfred Zimmermann
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  7. Dieter Bonke
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  8. Hugo H. Marti
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  9. Johannes Schenkel
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Correspondence to Johannes Schenkel.

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Tamer Rabie and Wolfgang Mühlhofer, as well as Hugo H. Marti and Johannes Schenkel contributed equally to this paper.

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Rabie, T., Mühlhofer, W., Bruckner, T. et al. Transient Protective Effect of B-Vitamins in Experimental Epilepsy in the Mouse Brain. J Mol Neurosci 41, 74–79 (2010). https://doi.org/10.1007/s12031-009-9286-4

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  • DOI: https://doi.org/10.1007/s12031-009-9286-4

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